Feeding behavior is an indispensable action for many organisms including humans. An abnormality in feeding behavior causes deviation from normal life support activities, which in most cases results in diseases. Along with the recent changes in feeding environments, obesity is becoming a social problem. It is widely known that obesity is not only a serious risk factor of life-style related diseases, such as diabetes, hypertension, arteriosclerosis and the like, but also causes arthritis and pain resulting from an excessive burden on knee joints etc. due to increased body weight. In addition, the dieting boom and the like have increased the potential population that desires weight loss. There are many reports on eating disorders, such as hyperphagia and the like, due to neuropathy and the like, which are genetic or caused by stress.
Consequently, the development and investigation of agents for the prophylaxis or treatment of obesity or feeding deterrents started some time ago, and mazindol has been on the market as a centrally acting anorectic agent.
Along therewith, a number of appetite-regulating factors represented by leptin have been found in recent years, and new anti-obesity agents and anorectic agents that suppress the activity of such appetite-regulating factors have been developed. Among others, a melanin-concentrating hormone is a hormone derived from hypothalamus and known to have an appetite stimulating action. Furthermore, MCH knockout mouse has been reported to show significantly decreased food intake and be lean, as compared to normal mouse, though normal in daily behavior [see Nature, vol. 396, p. 670, 1998]. From the foregoing, an MCH antagonist, once completed, is expected to be a superior anorectic agent or anti-obesity agent.
On the other hand, the following compounds are known as amine derivatives.
1) As β amyloid protein production and secretion inhibitor, a compound represented by the formula:
wherein    Ar is an aromatic group optionally having substituent(s);    X and Y are the same or different and each is a divalent group selected from —O—, —S—, —CO—, —SO—, —SO2—, —NR8—, —CONR8—, —SO2NR8— and —COO— (R8 is a hydrogen atom, a hydrocarbon group optionally having substituent(s) or an acyl) or a divalent C1-6 aliphatic hydrocarbon group optionally having one or two groups from these divalent groups;    R1 and R2 are a hydrogen atom or a C1-6 alkyl optionally having substituent(s), or R1 and R2 may form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom; and    ring A is a monocyclic aromatic ring optionally further having substituent(s),    or a salt thereof, has been reported (see WO00/31021).
2) As MCH antagonist, a compound represented by the formula:
wherein Ar1 is a cyclic group optionally having substituent(s);    X is a spacer having 1 to 6 atoms in a main chain;    Y is bond or a spacer having 1 to 6 atoms in a main chain;    Ar is a monocyclic aromatic ring optionally fused with a 4- to 8-membered non-aromatic ring, which optionally further has substituent(s); and    R1 and R2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 may form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom, R2 may form a spiro ring together with Ar, or R2 may form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom and Y,    or a salt thereof, has been reported (see WO01/21577).
3) As MCH antagonist, a compound represented by the formula:
wherein    Ar1 is a cyclic group optionally having substituent(s);    X and Y are the same or different and each is a spacer having 1 to 6 atoms in a main chain;    Ar is a fused polycyclic aromatic ring optionally having substituent(s); and    R1 and R2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 may form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom, R2 may form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom and Y, or R2 may form a fused ring together with the adjacent nitrogen atom, Y and Ar,    or a salt thereof, has been reported (see WO01/82925).
4) As cathepsin B substrate, a compound represented by the formula: Bz-X-Arg-MCA (Bz is a benzoyl group, MCA is a 7-methylcoumarinamido and X is a 4-aminomethyl-phenylalanine, a 4-guanidine-phenylalanine, a 4-aminomethyl-N-isopropylphenylalanine or the like), has been described (see Biochimica et Biophysica Acta, vol. 1547, pages 82-94, 2001).
5) It has been reported that an aminoalcohol derivative having a hypotensive, analgesic, antiinflammatory or psychotropic action is produced by the reaction shown in the scheme:
wherein    A is a straight chain or branched alkylene having 2 to 5 carbon atoms;    Y is —N(R4)(R5) [R4, R5 are the same or different and each is a hydrogen, a lower alkyl or an acyl] or —OR6 [R6 is a hydrogen, a lower alkyl, an aryl or an acyl];    R1 is a hydrogen or a lower alkyl;    R2 and R3 are the same or different and each is a hydrogen, a lower alkyl or an aralkyl, or a group forming a heterocycle together with the adjacent nitrogen atom; and    X is a hydrogen, a halogen or a lower alkyl (see JP51-141829A).
6) As an aminoalcohol derivative having a hypotensive, analgesic or psychotropic action, a compound represented by the formula:
wherein    R is an amino, a hydroxyl group, a lower alkoxy, an acyloxy, an aroyloxy, an acylamino or an aroylamino;    A is a lower alkylene;    R1 is a hydrogen or an acyl;    R2 is a hydrogen or a lower alkyl; and    ring P is a group forming, together with the nitrogen atom, a piperidine, a 4-substituted piperidine or a 4-substituted piperazine,    or an acid addition salt thereof, has been reported (see JP61-2663A).
7) As an aminoketone derivative having a hypotensive, analgesic, antiinflammatory or psychotropic action, a compound represented by the formula:
wherein    A is a straight chain or branched alkylene having 2 to 5 carbon atoms;    W is —N(R2)(R8) [R2 is a hydrogen or a lower alkyl; and R8 is a hydrogen or an acyl] or —OR4 [R4 is a hydrogen, a lower alkyl, an aryl or an acyl];    R1 is a hydrogen or a lower alkyl;    R5 and R6 are the same or different and each is a hydrogen, a lower alkyl or an aralkyl, or form, together with the adjacent nitrogen atom, a 1-pyrrolidinyl, a piperidino, a 4-carbamoyl-4-piperidinopiperidino, a 4-hydroxy-4-(p-tolyl)piperidino, a morpholino or a 4-substituted-1-piperazinyl; and    X is a hydrogen, a halogen or a lower alkyl,    or a salt thereof, has been disclosed (see JP51-141831A).
8) As a TNF-α-production suppressor and/or IL-10 production promoter, a compound represented by the formula:
wherein    Q is a group: X—Y [X is an amino optionally having substituent(s) or the like; and Y is an alkylene], or a heterocycle;    Z is an alkylene or the like;    R1 and R2 are a hydrogen, a halogen, an alkyl, an amino, a nitro or a hydroxyl group; and    R3 is a lower alkyl, an aryl, an aralkyl, a heteroaryl or a heteroaralkyl,    or a salt thereof, has been reported (see JP2001-72660A).
9) A compound useful for the treatment of inflammation, allergy and the like, which is represented by the formula:
wherein    R1 is a hydrogen, a halo, a cyano, a cyanoalkyl, an alkyl, an alkoxy, a phenoxy, a phenyl, an alkoxycarbonyl, —NR13R14, —N(R15)SO2R16, a halogenated alkoxy, a halogenated alkyl, an arylalkoxy, a hydroxyl group, a phenylalkyl, an alkoxycarbonylvinyl, —S(O)nR7, an alkoxycarbonylalkyl, a carboxyalkyl, —CONR11R12, a carbamoylvinyl, —OSO2R21, a 4,5-dihydrothiazol-2-yl, a 4,4-dimethyl-2-oxazolin-2-yl or —NR60R61; or R1 is —(O)z-L3G [z is 0 or 1; L3 is a C1-4 alkylene chain; and G is —NR22R23, —S(O)mR26, —CONR27R28 or —OR29];    R2 and R3 are independently a hydrogen, a halo, an alkyl, an alkoxy, —NR13R14, a halogenated alkoxy, a halogenated alkyl, a hydroxyl group, —S(O)nR7 or —NR60R61;    L1 is bond, an alkylene, a cycloalkylene or a cycloalkylidene;    T is bond, O, S, SO2, a carbonyl group or a 1,3-dioxolan-2-ylidene;    L2 is a alkylene, a cycloalkylene or a cycloalkylidene;    R6 is a hydrogen or an alkyl (optionally substituted by an alkoxycarbonyl or a hydroxyl group);    Q is a C1-9 alkylene chain (optionally substituted by an alkyl or a hydroxyl group); and    Y is an optionally substituted imidazole ring,    or a salt thereof, has been reported (see WO95/00493).